Why IV Ketamine is the Gold Standard for Treatment-Resistant Depression

About one in three people with major depressive disorder do not respond adequately to two or more antidepressant trials — a clinical pattern known as treatment-resistant depression (TRD) — and standard care guidelines were not built to address it (Gaynes et al., 2020). For these patients, the path forward requires a fundamentally different mechanism of action, not another medication from the same pharmacological family. At Thrive Center for Health in Grand Rapids, intravenous (IV) ketamine therapy represents that different approach — one supported by a growing body of clinical evidence and increasingly recognized as the most effective option available for TRD. Learn more about our unique depression treatment available in Grand Rapids, MI and what sets it apart from conventional care.

Why Standard Antidepressants Fall Short for TRD

Most first-line antidepressants — selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) — work by increasing the availability of serotonin or norepinephrine in the brain. For many people, this is enough. For those with treatment-resistant depression, it is not. The problem is not that these medications are ineffective in general; it is that TRD often involves neurobiological pathways that serotonin-targeted drugs do not directly address.

Research has increasingly focused on the glutamate system — the brain’s primary excitatory neurotransmitter network — as a central factor in cases where standard treatment fails. IV ketamine works by blocking N-methyl-D-aspartate (NMDA) receptors in this system, producing antidepressant effects through a mechanism entirely distinct from SSRIs and SNRIs (Zanos & Gould, 2018). This is not a variation on existing treatment; it is a different pharmacological target altogether.

The clinical results reflect that difference. Studies show ketamine produces rapid and significant antidepressant effects in patients with treatment-resistant major depression who have not responded to multiple prior medications (Murrough et al., 2013). At our clinic, approximately 70–75% of patients report a favorable outcome — a figure consistent with what the broader research literature has documented for this population. For a deeper look at how this mechanism plays out neurologically, see our post on ketamine effective in treatment-resistant depression.

The Speed Advantage: Hours, Not Weeks

One of the most clinically meaningful distinctions between IV ketamine and traditional antidepressants is the timeline. SSRIs typically require four to six weeks at therapeutic doses before patients notice a meaningful change in mood. For someone in the depths of treatment-resistant depression, six weeks is not an abstraction — it is six more weeks of impaired function, strained relationships, and diminished quality of life.

Ketamine operates on a different timeline. The National Institute of Mental Health (NIMH) has highlighted research showing ketamine restores pleasure-seeking behavior — one of the core symptoms depression erodes — ahead of other antidepressant effects, suggesting it targets the neurobiology of depression quickly and directly (NIMH, 2014). Many of our patients begin to notice changes within hours of their first infusion. Some require multiple sessions before experiencing significant relief, and results vary by individual — but the speed of action in responders represents a meaningful clinical advantage that no other currently available oral antidepressant can match.

The NIMH has also recognized ketamine as a rapid-acting depression treatment offering new hope specifically for patients who have not responded to standard care (NIMH, 2024). This is not fringe science. It is the direction psychiatric medicine is moving. To understand more about what happens in the brain during treatment, read our overview of how ketamine affects the brain.

What IV Administration Means for TRD Treatment

The intravenous route matters. When ketamine is delivered directly into the bloodstream through an IV, it bypasses the digestive system entirely, allowing for precise dosing and consistent absorption that oral or intranasal formulations cannot replicate with the same reliability. SPRAVATO® (esketamine), the FDA-approved nasal spray, offers one alternative for TRD — but it is a different compound, delivered differently, and approved under specific clinical protocols that may not apply to every patient.

IV ketamine infusions remain off-label for depression, which is worth understanding clearly: off-label does not mean experimental or unproven. It means the FDA approval pathway has not been pursued for this specific delivery method, even as the clinical evidence base has continued to grow. Our providers make this distinction explicit during the screening and consultation process so that every patient has an accurate picture of what they are considering.

Our Protocol and What to Expect

At Thrive Center for Health, the standard initial series for mood disorders consists of 6–10 infusions, with the psych clearance and medical clearance steps completed before any infusions begin. The clearance process serves a clinical purpose: it establishes whether ketamine is appropriate for each individual patient based on their psychiatric and medical history. Our team — led by board-certified Psychiatric Mental Health Nurse Practitioners Erika and Kari, both ASKP3-trained, and overseen by Medical Director Dr. Drumm, a General Psychiatrist with ketamine clinical research experience from his residency — uses this process to confirm candidacy and build a personalized treatment plan.

Each infusion session runs approximately one to one and a half hours, including a recovery period before you leave our care. We do not rush that process. You remain with us until it is safe to go home. For a fuller picture of what a session involves, our post on ketamine infusion therapy: the patient experience walks through exactly what patients encounter from arrival to discharge.

For patients who respond to the initial series, maintenance infusions are available on a weekly or monthly basis as needed. The research supports this approach: studies show that both single and repeated infusions can address treatment-resistant depression, and maintenance infusions extend the duration of benefit for patients who respond well (Murrough et al., 2018).

Addressing the Cost Question

We understand that cost is a real consideration. Without accepted insurance, the psych clearance is $250, medical clearance is $150, and each infusion in the initial series is $500. For patients with accepted insurance — including Cigna, BCBS, Priority Health, Aetna, McLaren, Molina, TriCare, Michigan Medicaid, and Michigan Medicare — the cash portion per infusion drops to $300, with office visit components billed to insurance. A $40 deposit is required at scheduling for insured patients. Full details on fees and accepted plans are available on our pricing page.

Veterans receive a 10% discount on all visits. Monthly support group meetings are included at no charge for all patients. We also require a credit card on file for all patients, and our cancellation policy charges $150 for appointments canceled with less than 24 hours’ notice, with exceptions for medical and family emergencies.

If you have questions about what your specific plan covers, contact us before scheduling — our team will work through the insurance details with you so there are no surprises.

Frequently Asked Questions

What does “treatment-resistant depression” actually mean? Treatment-resistant depression is a clinical designation for major depressive disorder that has not responded adequately to at least two antidepressant medications at appropriate doses and for an appropriate duration — typically six to eight weeks each. It is a specific clinical threshold, not a general description of depression that is hard to treat. If you are unsure whether your history meets that definition, our evaluation process will clarify it.

Is IV ketamine the same as SPRAVATO®? No. SPRAVATO® is an FDA-approved nasal spray containing esketamine, a derivative of ketamine, approved specifically for treatment-resistant depression. IV ketamine uses a different formulation, delivered intravenously, and is considered an off-label treatment. Both work through the glutamate system, but they are distinct compounds delivered through different routes under different clinical protocols. Our providers can discuss which approach may be appropriate for your situation.

How many infusions will I need before I feel a difference? The initial series at our clinic consists of 6–10 infusions. Some patients notice changes after the first session; others require several infusions before experiencing meaningful relief. Results vary by individual, and our team monitors your response closely and adjusts your dose as needed across sessions.

Will I need to stop my current antidepressants? Not necessarily. Whether you continue existing medications alongside ketamine therapy depends on your individual history and how you respond to treatment. This is a clinical decision made collaboratively with your provider — not a blanket policy. Our team reviews your current medications as part of the clearance process.

What does the consultation cost, and is it covered by insurance? The initial psych clearance is $250 without insurance. For patients with accepted insurance, the office visit component is billed to insurance and the cash portion is $0 upfront, though you are responsible for what insurance does not cover. A $40 deposit is required at scheduling for insured patients.

Key Takeaways

• Treatment-resistant depression is defined as inadequate response to two or more antidepressant trials at therapeutic doses — it is a clinical designation with a specific threshold, not a general description of difficult-to-treat depression.
• IV ketamine works through the glutamate system via NMDA receptor blockade, a mechanism entirely distinct from SSRIs and SNRIs, which is why it may help patients for whom standard antidepressants have not worked.
• Clinical research consistently documents rapid antidepressant effects in TRD patients, with many people noticing changes within hours rather than the weeks required by traditional medications.
• The standard initial series at Thrive Center for Health consists of 6–10 infusions with psych and medical clearance completed first; maintenance infusions are available as needed following the initial series.
• Insurance coverage, including several Michigan-based plans, may reduce out-of-pocket costs significantly — contact our team to verify your specific coverage before scheduling.

When antidepressants have not worked, that history is clinical information, not a verdict on whether recovery is possible. At Thrive Center for Health in Grand Rapids, we start every evaluation by taking that history seriously and asking what it tells us about where to go next. If you are ready to explore whether IV ketamine therapy may be right for you, call us at 616-730-8069 or schedule a consultation through our website. We will give you a straight answer about your options.

References

Murrough, J. W., Iosifescu, D. V., Chang, L. C., Al Jurdi, R. K., Green, C. E., Perez, A. M., Iqbal, S., Pillemer, S., Foulkes, A., Shah, A., Mathew, S. J., & Charney, D. S. (2013). Antidepressant efficacy of ketamine in treatment-resistant major depression: A two-site randomized controlled trial. American Journal of Psychiatry, 170(10), 1134–1142. https://pubmed.ncbi.nlm.nih.gov/23982301/

Murrough, J. W., Perez, A. M., Pillemer, S., Stern, J., Parides, M. K., aan het Rot, M., Collins, K. A., Mathew, S. J., Charney, D. S., & Iosifescu, D. V. (2018). Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. American Journal of Psychiatry, 175(5), 424–433. https://psychiatryonline.org/doi/10.1176/appi.ajp.2018.18070834

National Institute of Mental Health. (2014). Rapid agent restores pleasure-seeking ahead of other antidepressant action. https://www.nimh.nih.gov/news/science-updates/2014/rapid-agent-restores-pleasure-seeking-ahead-of-other-antidepressant-action

National Institute of Mental Health. (2024). New hope for rapid-acting depression treatment. https://www.nimh.nih.gov/news/science-updates/2024/new-hope-for-rapid-acting-depression-treatment

Medical Disclaimer

The information in this blog is provided for educational purposes only and does not constitute medical advice. Ketamine therapy, including IV ketamine infusions, should only be pursued under the supervision of a licensed medical provider familiar with your full psychiatric and medical history. Individual results vary — not every patient will respond to ketamine therapy, and no specific outcome can be guaranteed. If you are experiencing a mental health crisis or thoughts of self-harm, please call or text 988 to reach the Suicide and Crisis Lifeline or go to your nearest emergency room. Please discuss all treatment options with a qualified healthcare provider before making any decisions about your care.